Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study

Neuroreport
Vincent J HuberTsutomu Nakada

Abstract

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in additio...Continue Reading

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Citations

Dec 19, 2018·ELife·Humberto MestreMaiken Nedergaard
Aug 13, 2020·Molecular Neurobiology·Gabriela-Camelia RosuPirici Daniel
May 26, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Tsutomu Nakada, Ingrid L Kwee
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Aug 13, 2020·Korean Journal of Radiology : Official Journal of the Korean Radiological Society·Toshiaki Taoka, Shinji Naganawa
Feb 23, 2021·Reviews in the Neurosciences·Galina YankovaAndrey Tulupov
Apr 16, 2021·JCI Insight·Mohammed S AlshuhriWilliam M Holmes
Jun 23, 2021·Radiology·Yoshimi Anzai, Satoshi Minoshima
Nov 29, 2020·Neuroscience·Helene BenvenisteNora D Volkow
Nov 16, 2021·Frontiers in Cellular Neuroscience·Adonis SferaZisis Kozlakidis

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Methods Mentioned

BETA
nuclear
proton exchange
nuclear magnetic resonance
NMR

Software Mentioned

MR vision
SPSS

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